Enhanced antitumor efficacy of folate‐linked liposomal doxorubicin with TGF‐β type I receptor inhibitor

Taniguchi, Yukimi; Kawano, Keiichi; Minowa, Takuya; Sugino, Takashi; Shimojo, Yuki; Maitani, Yoshie

doi:10.1111/j.1349-7006.2010.01646.x

Cited by 25 publications

(19 citation statements)

References 22 publications

(40 reference statements)

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“…Moreover, no significant difference in antitumor activities was found between PBS, DOX·HCl, and DOX/SA micelles ( P > 0.1). This is likely due to the low doses of DOX (2 mg/kg), as compared with the dose of 8~10 mg/kg used for the treatment of M109 tumors in previous reports [41, 42]. Despite the low DOX dosage, our DS micelles demonstrated high antitumor activity.…”

Section: Iii) Resultsmentioning

confidence: 79%

Blood-stable, tumor-adaptable disulfide bonded mPEG-(Cys)4-PDLLA micelles for chemotherapy

et al. 2013

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Although targeted delivery mediated by ligand modified or tumor microenvironment sensitive nanocarriers has been extensively pursued for cancer chemotherapy, the efficiency is still limited by premature drug release after systemic administration. Herein we report a highly blood-stable, tumor-adaptable drug carrier made of disulfide (DS) bonded mPEG-(Cys)4-PDLLA micelles. Intravenously injected disulfide bonded micelles stably retained doxorubicin in the bloodstream and efficiently delivered the drug to a tumor, with a 7-fold increase of the drug in the tumor and 1.9-fold decrease in the heart, as compared with self-assembled (SA), non-crosslinked mPEG-PDLLA micelles. In vivo administration of disulfide bonded micelles led to doxorubicin accumulation in cancer cell nuclei, which was not observed after administration of self-assembled micelles. With a doxorubicin dose as low as 2 mg/kg, disulfide bonded micelles almost completely suppressed tumor growth in mice.

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Section: Iii) Resultsmentioning

confidence: 79%

Blood-stable, tumor-adaptable disulfide bonded mPEG-(Cys)4-PDLLA micelles for chemotherapy

et al. 2013

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“…For example, targeting TGF-β signaling can enhance the therapeutic efficacy of various cytotoxic agents as was recently shown for rapamycin [170] and doxorubicin [171,172]. Unpublished studies in our laboratory show that SD-208 dosed in combination with an inhibitor of bone resorption, zoledronic acid, reduces the progression of established osteolytic metastases from breast cancer more effectively than either therapy alone [173].…”

Section: Combination Therapymentioning

confidence: 76%

TGF-β in the Bone Microenvironment: Role in Breast Cancer Metastases

Buijs

Stayrook

Guise

2011

Cancer Microenvironment

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Breast cancer is the most prevalent cancer among females worldwide. It has long been known that cancers preferentially metastasize to particular organs, and bone metastases occur in ∼70% of patients with advanced breast cancer. Breast cancer bone metastases are predominantly osteolytic and accompanied by bone destruction, bone fractures, pain, and hypercalcemia, causing severe morbidity and hospitalization. In the bone matrix, transforming growth factor-β (TGF-β) is one of the most abundant growth factors, which is released in active form upon tumor-induced osteoclastic bone resorption. TGF-β, in turn, stimulates bone metastatic cells to secrete factors that further drive osteolytic destruction of the bone adjacent to the tumor, categorizing TGF-β as a crucial factor responsible for driving the feed-forward vicious cycle of cancer growth in bone. Moreover, TGF-β activates epithelial-to-mesenchymal transition, increases tumor cell invasiveness and angiogenesis and induces immunosuppression. Blocking the TGF-β signaling pathway to interrupt this vicious cycle between breast cancer and bone offers a promising target for therapeutic intervention to decrease skeletal metastasis. This review will describe the role of TGF-β in breast cancer and bone metastasis, and pre-clinical and clinical data will be evaluated for the potential use of TGF-β inhibitors in clinical practice to treat breast cancer bone metastases.

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“…Polyethylene glycol (PEG) functions as the outer corona and prolongs the circulation time of the NPs in blood by reducing non-specific interactions with blood components [9–17]. The PLGA hydrophobic component serves as a reservoir for lipophilic drug, while the anionic component provides the ability to strong electrostatic interaction with cationic drugs [18, 19]. However, the biodistribution of K237/FA-PEG-PLGA NPs has not yet been specifically and quantized studied in ovarian cancer model by using radioisotope 99m Tc.…”

Section: Introductionmentioning

confidence: 99%

Immune activity and biodistribution of polypeptide K237 and folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles radiolabeled with 99mTc

Zhang

Huang

et al. 2016

Oncotarget

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In a previous study, amphiphilic copolymer, polypeptide K237 (HTMYYHHYQHHL) and folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (K237/FA-PEG-PLGA) nanoparticles were developed and studied as a drug carrier. To further promote the clinical application of K237/FA-PEG-PLGA nanoparticles and provide guidance for future research, we need to examine their specific biodistribution in vivo. In this study, K237/FA-PEG-PLGA nanoparticles were effectively labeled by a direct method with Technetium-99m (99mTc) using stannous chloride as a reducing agent. The optimal stability of the labeled nanoparticles was determined by evaluating their radiochemical purity in serum, physiological saline, diethylenetriaminepentaacetic acid (DTPA) and cysteine solutions. The affinity of ligands and receptors was elicited by cell binding and blocking experiments in KDR/folate receptor high expressing SKOV-3 ovarian cancer cells. The nanoparticles biodistribution was studied after intravenous administration in healthy mice xenografted with SKOV-3 cells. A higher percent injected dose per gram of tissue (% ID/g) was observed in liver, kidney, spleen, blood and tumor at 3 and 9 h post-injection. Scintigraphic images revealed that the radioactivity was mainly concentrated in tumor, liver, kidney and bladder; and in the heart, lung, and muscle was significantly lower at 3 h. The radioactivity distribution in the images is consistent with the in vivo biodistribution data. Our works demonstrated that K237/FA-PEG-PLGA nanoparticles have great potential as biodegradable drug carriers, especially for tumors expressing the folate and KDr receptor.

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Enhanced antitumor efficacy of folate‐linked liposomal doxorubicin with TGF‐β type I receptor inhibitor

Cited by 25 publications

References 22 publications

Blood-stable, tumor-adaptable disulfide bonded mPEG-(Cys)4-PDLLA micelles for chemotherapy

Blood-stable, tumor-adaptable disulfide bonded mPEG-(Cys)4-PDLLA micelles for chemotherapy

TGF-β in the Bone Microenvironment: Role in Breast Cancer Metastases

Immune activity and biodistribution of polypeptide K237 and folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles radiolabeled with 99mTc

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